PROJECT SUMMARY/ABSTRACT?Hematological Malignancies Program The overall goal of the Hematological Malignancies Program (HMP) is to advance cure rates for pediatric leukemias and lymphomas while reducing toxicity of therapy. The HMP is an established, highly interactive, transdisciplinary program with a long track record of major discoveries in cancer biology, and the translation of these into new diagnostic and treatment approaches that have changed the standard of care of pediatric hematological malignancies. Charles Mullighan, MBBS (Hons), MD (laboratory lead) and Ching-Hon Pui, MD (clinical lead) are jointly responsible for the academic themes and direction of the Program. They bring together expertise spanning the basic-to-clinical spectrum that significantly enhances HMP activities and facilitates national and international collaborations. They align research efforts of the HMP with strategic goals of the SJCCC and identify inter-programmatic collaborative opportunities. HMP members participate in multiple intra- programmatic meetings and seminar series that facilitate transdisciplinary research, clinical, and educational activities. Program activities are organized into 3 working groups: Basic, Translational, and Clinical Research Groups. The HMP has 19 Full Members and 6 Associate (junior mentored) Members, including 3 members each of the National Academy of Medicine and the Association of American Physicians, 3 Fellows of the American Association for the Advancement of Science, and 5 members of the American Society for Clinical Investigation. Members are drawn from the Departments of Pediatric Medicine, Hematology, Infectious Diseases, Oncology, Pathology, Bone Marrow Transplantation & Cellular Therapy, and Pharmaceutical Sciences. HMP members have a total of $4.4M in annual peer-reviewed funding, including $2M in NCI funding and $1.6M in other NIH funding. Research from the HMP has resulted in 578 publications, of which 33.1% are intra-programmatic, 35.5% are inter-programmatic, and 77.5% are inter-institutional (many with other NCI-designated Cancer Centers). In addition, a total of 5 multi-investigator grants were awarded to the Program, two of which are inter-programmatic with CBP (P50GM115279) and CCSP and NBTP (U01CA195547). During the funding period (2013-2017) the HMP contributed 1134 interventional enrollments of which 1045 were therapeutic enrollments. By comparison, in the prior period (2008-2012) HMP had 973 interventional enrollments of which 885 were therapeutic. In addition, HMP contributed to the Center's overall transprogrammatic non-interventional studies totaling 30,071 accruals during the funding period. This includes 438 unique participants in specific HMP investigator driven non-interventional studies. During the current funding period, the HMP focused on common and clinically problematic hematological malignancies, including ALL, acute myeloid leukemia (AML), and relapsed leukemia. The Program also enriched research efforts in important but less well-characterized diseases, including infant leukemia, pediatric myelodysplasia, and lymphoma. HMP accomplishments have had national and global impact in the diagnosis, classification, and treatment of hematological malignancies.